A recent study published in the Annals of Internal Medicine investigated the challenges and solutions associated with the unbiased estimation of post coronavirus disease 2019 (COVID-19) sequelae.

Various studies have reported cases of Long-COVID or post-acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) syndrome (PASC). However, there is insufficient information about the characteristics and diagnosis of Long-COVID. Hence, PASC-related studies need to be more robust considering their long-term impact under the continuously evolving conditions of the COVID-19 pandemic.

Study: Toward Unbiased Evaluation of Postacute Sequelae of SARS-CoV-2 Infection: Challenges and Solutions for the Long Haul Ahead. Image Credit: Donkeyworx / ShutterstockStudy: Toward Unbiased Evaluation of Postacute Sequelae of SARS-CoV-2 Infection: Challenges and Solutions for the Long Haul Ahead. Image Credit: Donkeyworx / Shutterstock

About the study 

The present study assessed the various challenges and potential solutions in the diagnosis and management of sequelae in Long-COVID or PASC.

Detailed diagnosis and treatment schedules must be prepared to ensure that PASC patients receive appropriate disease monitoring, timely support, and eventual treatment courses. This is especially important due to the difficulty of differentiation between post-intensive care syndrome and PASC.

Notably, many characteristic symptoms of PASC can be self-perceived rather than being confirmed by laboratory tests for SARS-CoV-2 infection. This highlights the importance of thoroughly evaluating the presenting symptoms and their correlation to the virus. However, such assessments are time-consuming, expensive, and lack uniform application of criterion standards.

Problems of bias in the study design like the recall bias and the surveillance bias may affect the patient’s medical reports. Also, heightened lay attention could affect the degree to which the patients remember the onset and duration of symptoms. This requires the application of robust, longitudinal, and standardized assessments of patient well-being and health across all systems to facilitate real-time comparison and monitoring of symptoms.

Notably, patients most vulnerable to the impact of the COVID-19 pandemic belong to the socioeconomically burdened populations. Due to the prevalence disparities in these populations, the inequities in the presentation, development, and documentation of PASC might be highlighted. This social disparity also calls for accurate diagnostic testing and documentation of symptoms in these patients’ clinical records in order to ascertain PASC across groups of different vulnerabilities.

The assessment of the risk of PASC among populations could be refined using appropriate comparator groups. Furthermore, drawing comparisons between long-term symptoms post SARS-CoV-2 infections versus post influenza infections may help eliminate selection effects caused by the lack of access to diagnostic testing in the vulnerable populations.


The researchers of the present study suggested the following actions for the medical community. First, they need to formulate a distinct and measurable definition for PASC that allows consistent application across all populations. They can also focus on implementing standardized and robust approaches towards the measurement of potential PASC risk factors and outcomes.

Thorough descriptions of symptoms obtained via questions tailored to assess the incidence of symptoms should be used to reduce recall bias and establish clear temporal ordering. Surveillance bias could be controlled by enabling standardized data collection of symptoms before and after the onset of COVID-19. Also, selection bias could be handled by being mindful of the various socioeconomic disparities which could influence PASC-related characteristics. Partnering with the community for research as well as recruiting from the respective community settings can further reduce selection bias.

The researchers believed that deriving information that is consistent and of high quality based on diverse study designs is crucial in improving the medical community’s understanding of PASC and its ability to handle and prevent it.


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